Implant for deep sclerectomy

ABSTRACT

The invention concerns an implant for deep sclerectomy for draining aqueous humor during surgical treatment of glaucoma. The implant is made of crosslinked hyaluronic acid and has substantially the shape of a polyhedron with at least five faces, advantageously the shape of a polyhedron with five or six faces. In a preferred embodiment, the implant has substantially the shape of a prism, advantageously straight with a trapezoidal base.

The present invention relates to an implant for deep sclerectomy. Saidimplant of the invention is characterized by the material constitutingit and by its shape.

The surgical technique of deep sclerectomy has been proposed recentlyfor treating glaucoma. In effect, when the glaucoma connot be treatedmedically, it is necessary to intervene surgically to reduce theintraocular pressure.

The most current operatory technique is trabeculotomy. Saidtrabeculotomy consists in making an opening through the trabeculum, inorder to evacuate the aqueous humor from the anterior chamber towardsthe subconjunctival space. A filtration bulla then generally appearsbeneath the conjunctiva 3, provoked by the accumulation of said aqueoushumor beneath said conjunctiva. The complications associated with thissurgical technique are fairly numerous. They consist in precocious orlate hypotoniae, in reductions in depth of the anterior chamber and evenin the collapse thereof, in a choroidal lift . . . One of the mostdramatic complications is the secondary rupture of said filtrationbulla, which may cause an endophthalmitis.

In order to avoid opening the anterior chamber 8, other surgicaltechniques have been proposed. One of these techniques, within theframework of which the present invention is included, is deep (so-callednon-perforating) sclerectomy of the glaucoma. It consists in incisingthe sclera 2 until plumb with Schlemm's canal 7. The aqueous humor thengushes through the trabeculum 6. In order to assist the flow of saidaqueous humor, it has been proposed to place, in said incision (in thedeep scleral bed), a collagen implant, cylindrical in shape (theanterior end of said implant, opposite Schlemm's canal 7). Said implantfacilitates said flow of said aqueous humor, performing the role of awick (it transports the ocular fluids by capillarity). Results ofimplementation of this technique (deep sclerectomy associated with theplacing of a collagen implant), of which the principle is recalled, arepresented in Ophtalmologie 1995; 9: 666-670. A great future does notseem promised for said implant, due to its shape and the nature of thematerial consituting it. In effect, the cylindrical shape is not theshape most adapted to the anatomy of the eye and the materialused—collagen of animal origin—is no longer recommended in view of theproblems associated with the Creutzfeldt-Jakob syndrome.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a partial cross-sectional side view illustrating placement ofone embodiment of the invention in the sclera of the eye;

FIG. 1A is a partial cross-sectional side view illustrating placement ofanother embodiment of the invention in the sclera of the eye;

FIG. 2 is a perspective view illustrating one embodiment of theinvention; and

FIG. 2A is a perspective view illustrating another embodiment of theinvention.

The applicant is at present proposing an implant 1 which, within theframework of this surgical technique of (non-perforating) deepsclerectomy with implant, advantageously replaces said collagen implant,of cylindrical shape, of the prior art. Said implant of the invention asshown in FIGS. 1 and 1A—thanks to the characteristics of the materialconstituting it and to its geometrical shape—occupies for a longerperiod the space created surgically and efficiently allows the flow ofthe aqueous humor from the anterior chamber (without opening thelatter); it constitutes a veritable drain.

Said implant 1 of the invention—implant for deep sclerectomy intended todrain the aqueous humor—is made of crosslinked hyaluronic acid andpresents substantially the shape of a polyhedron with at least fivefaces. Advantageously, it presents substantially the shape of apolyhedron with five or six faces.

Such a polyhedral implant which therefore presents at least five speciesis relatively blocked once positioned in the space created; said implantfurther presenting, of course a volume adapted to the volume of saidspace. It should be possible to insert it in said space and then have itperform its function of wick, of veritable drain.

The person skilled in the art will understand the qualifying adverb“substantially” employed with reference to the shape of the implants ofthe invention perfectly well, in view of the nature of the materialconstitutint them. We shall return to said material hereinbelow in thepresent text.

Said implants of the invention advantageously present substantially theshape of a convex polyhedron, with at least five faces; said convexpolyhedron having at least one substantially plane base (whichconstitutes its face or one of its faces of largest surface) whichpresents at least 3 sides and a small thickness. Thickness of saidimplants of the invention is understood to mean the maximum distancebetween said base and the apex opposite or the face opposite said base.Said thickness—small, generally included between 0.2 and 2 mm—isadvantageously included between {fraction (1/12)}th and ¼ (preferablybetween {fraction (1/10)}th and ⅛th of the length of the largest side ofsaid base (with at least 3 sides).

Said (substantially plane) base, defined by a polygon with at leastthree sides, advantageously consists in a triangle or a quadrilateral,more particularly in a, trapezium (preferable isosceles) as shown inFIG. 2 and 2A.

Said “substantially” plane base (by the nature of the materialconstituting the implant) is, however, advantageously slightly incurvedso that, once the implant is positioned, it follows the radius ofcurvature of the eye. According to this advantageous variant, itssurface is therefore slightly concave.

Within the scope of advantageous variants of the invention, the implantspresent substantially:

the shape of an advantageously straight prism, with trapezoidal base(the trapezium of the base of such a prism is preferably an isoscelestrapezium) or triangular; or

the shape of a parallelepiped, advantageously a straight parallelepiped,and preferably a rectangular parallelepiped.

It is clear that, according to other variants, said polyhedral implantsmay present other shapes and in particular those of pyramids withrectangular or square base, those of such pyramids truncated, those ofprisms, particularly straight ones, with any base . . .

It is recalled here that, generally, the base of the implant 1 of theinvention (at least one of them; intended to be positioned alongDescemet's membrane 5 and the internal wall of the sclera 2) isadvantageously slightly incurved.

Furthermore, likewise generally, the angles of the polyhedronconstituting the implant of the invention are advantageously blunt. Thismay constitute an advantage with reference to possible problems oftraumatisms.

We shall now come to the nature of the material constituting theimplants of the invention. It is question of crosslinked hyaluronicacid, sufficiently crosslinked to constitute a solid implant.

Hyaluronic acid is a glycosaminoglycan or mucopolysaccharide of highmolecular weight which is found in animal tissues such as umbilicalcords, the vitreous humor, the synovial liquid, condylomas, the skin,connective tissues (joints, tendons . . . ) . . . Said acid may thus beobtained naturally by extraction from certain of said animal tissues (inparticular the condylomas and umbilical cords). It may also be obtainedby bacterial fermentation. Said acid presents a high propensity forabsorbing water. It is a very hydrophilic material whose water content,at equilibium, is greater than 99%. Said material is perfectly suitablefor ensuring the function of drain desired for the implant of theinvention.

The chemical structure of said acid is that of a polymer presentingdisaccharidic monomers of N-acetyl-D-glucosamine and of D-glucoronicacid, said amine and said acid being connected by a glucosidic β1→3bond. The disaccharidic monomers are connected together by glucosidicβ1→4 bonds in order to generate the non-crosslinked polysaccharidicchain without branching.

However, said chain presents, at the level of its monomers, functions,particularly hydroxyl ones, which allow it to be crosslinked chemicallyin order to create a more or less dense network.

In the present text and claims which accompany it, the term hyaluronicacid is employed as a generic name for designating both hyaluronic acidper se and its salts, particularly salts of hyaluronate. The implants ofthe invention are therefore based on a polymer selected from crosslinkedhyaluronic acid and the crosslinked salts of said acid. Advantageously,they are based on crosslinked sodium hyaluronate. Said interveningsodium hyaluronate is advantageously of bacterial origin.

Said hyaluronic acid intervenes, within the framework of the invention,solid, crosslinked at a sufficient rate of crosslinking. It isrecommended to carry out said crosslinking, via the hydroxyl functionsof said acid, by means of a crosslinking agent presenting reactivefunctions; said agent intervening in quantities such that the ratio:total number of reactive functions of said crosslinking agent(intervening in the reactional medium)/total number of disacchariderepeating units of the molecules of hyaluronic acid (present in thereactional medium) is included between 0.2 and 1.

A minimum crosslinking assures the desired effect: the obtaining of asolid, presenting minimum mechanical resistance.

A maximum crosslinking is advantageously not exceeded. In effect, theintervention of a large quantity of crosslinking agent denatures theimplants of the invention.

By way of crosslinking agent, there may be used, for making the implantsof the invention, any agent known for crosslinking the hyaluronic acidvia its hydroxyl functions—at least bifunctional crosslinking agent—andin particular a polyepoxide or its derivatives. By way of such acrosslinking agent, there may be used in particular epichlorhydrine,divinylsulfone, 1,4-bis(2,3-epoxypropoxy)butane (or1,4-bis(glycidyloxy)butane or 1,4-butanediol diglycidyl ether=BDDE),1,2-bis(2,3-epoxypropoxy)ethylene, 1-(2,3-epoxypropyl)-2,3-epoxycyclohexane . . . Numerous crosslinking agents suitable for carrying outcrosslinking of hyaluronic acid have been described in particular inU.S. Pat. No. 4,716,154.

It is not excluded from the scope of the invention to employ a pluralityof crosslinking agents in order to obtain a crosslinked hyaluronic acidin which an implant of the invention is cut.

According to an advantageous variant, a crosslinking agent whosereactive functions are epoxy functions is used for preparing saidcrosslinked hyaluronic acid.

Generally, the carrying out of crosslinking of hyaluronic acid (or ofone of its salts) is a familiar process for the person skilled in theart.

Originally, within the scope of the present invention, said crosslinkedhyaluronic acid is used for producing polyhedral implants with at leastfive faces, suitable by way of implants for deep sclerectomy. Saidimplants are very hydrophilic due to the material constituting them andefficiently ensure evacuation of the aqueous humour from the anteriorchamber.

The implants of the invention—polyhedrons with at least 5 faces, made ofcrosslinked hyaluronic acid—possibly have at least one active principleincorporated therein. Said active ingredient may in particular consistof an antibiotic and/or an antimitotic. There is no particulardifficulty in incorporating active principle(s) in the mass of saidimplants of the invention. This is generally carried out during a stepof hydration of said implants.

Finally, the implants of the invention are obtained by cutting out theadequate shape from a block of crosslinked hyaluronic acid. As saidblock generally presents a small thickness, we speak rathermore oflamella. The implants of the invention are positioned without particulardifficulty through an adequate incision. Said incision was previouslymade to produce the space or cavity for implantation.

The present invention also covers an original application—by way ofimplant for deep sclerectomy, intended to drain the aqueous humour—of asubstantially polyhedral mass with at least five faces (advantageouslywith five or six faces), made of crosslinked hyaluronic acid.

In fact, it also has for an object:

an original use of the crosslinked hyaluronic acid for the production ofan implant for deep sclerectomy, presenting substantially the shape of apolyhedron with at least five faces, advantageously substantially theshape of a polyhedron with five or six faces; implant intended to drainthe aqueous humour;

the carrying out of deep sclerectomy—non-perforating surgery of theglaucoma—with the intervention of an implant, in the above-mentionedmaterial, of the above-mentioned shape.

In order to illustrate, in non-limiting manner, the invention presentlyclaimed, an example of preparation of implants of the invention isattached to the above description.

The protocol followed is as follows:

1.00 g of sodium hyaluronate (with a molecular mass of 2.10⁶ Da) isdissolved in 7.80 g of an aqueous 0.25 M sodium hydroxide solution;

0.192 g of BDDE (crosslinking agent: 1,4-butanediol diglycidyl ether)are added to the solution;

after homogenization, the latter is placed in a water bath at 50° C. for2 hours,

a solid gel is then obtained which is hydrated up to equilibrium indeionized water;

said gel is then purified by continuous extraction, by de-ionized water,in a Soxhlet apparatus;

the gel thus purified is placed in equilibrium in a phosphate buffersolution at pH 7.2;

lamellae of 0.5 mm thickness are then cut out therefrom;

finally, these lamellae are bored into, with the aid of a bit presentinga trapezoidal cross-section (isosceles trapezium of which the basesmeasure respectively 3 and 0.5 mm and the height 5 mm); implants arethen obtained which have substantially the shape of straight prisms withtrapezoidal base and whose thickness varies between 0.5 and 1 mm.

What is claimed is:
 1. An implant for deep sclerectomy, intended todrain the aqueous humor, made of crosslinked hyaluronic acid andpresenting substantially the shape of a polyhedron with at least fivefaces wherein at least one face is structured to direct flow of theaqueous humor.
 2. The implant of claim 1, wherein it presentssubstantially the shape of a polyhedron with five or six faces.
 3. Theimplant of claim 1, wherein it presents substantially the shape of aconvex polyhedron; said convex polyhedron having at least asubstantially plane base which presents at least 3 sides and a smallthickness; said thickness being defined as the maximum distance betweensaid base and an apex opposite or a face opposite said base.
 4. Theimplant of claim 3, wherein said thickness is included between {fraction(1/12)}th and ¼ of the length of the largest side of said base.
 5. Theimplant of claim 3, wherein said base has a triangular or trapezoidalshape.
 6. The implant of claim 3, wherein said base is slightly incurvedso that, once the implant is positioned, it follows a radius ofcurvature of the eye.
 7. The implant of claim 1, wherein it presentssubstantially the shape of a prism with trapezoidal base.
 8. The implantof claim 7, wherein it presents substantially the shape of a straightprism with trapezoidal base.
 9. The implant of claim 1, wherein itsapices are blunt.
 10. The implant of claim 1, wherein said hyaluronicacid has been crosslinked, via its hydroxyl functions, by means of acrosslinking agent presenting reactive functions; said agent interveningin quantities such that the ratio: total number of reactive functions ofsaid crosslinking agent/total number of disaccharidic repeating units ofthe molecules of hyaluronic acid, is included between 0.2 and
 1. 11. Theimplant of claim 10, wherein said reactive functions of saidcrosslinking agent are epoxy functions.
 12. The implant of claim 1,wherein said crosslinked hyaluronic acid has at least one activeprinciple incorporated therein.
 13. The implant of claim 1, wherein itsthickness is about 2 mm.
 14. A method for treating glaucoma according tothe surgical technique of deep sclerectomy carried out with an implant,said method comprising incising the sclera until plumb with Schlemm'scanal to generate a cavity in the deep scleral bed, inserting in saidcavity an implant, wherein said implant is made of crosslinkedhyaluronic acid and presents substantially the shape of a polyhedronwith at least five faces.
 15. The method of claim 14, wherein saidimplant presents substantially the shape of a polyhedron with five orsix faces.
 16. The method of claim 14, wherein said implant presentssubstantially the shape of a convex polyhedron; said convex polyhedronhaving at least a substantially plane base which presents at least 3sides and small thickness; said thickness being defined as the maximumdistance between said base and an apex opposite or a face opposite saidbase.
 17. The method of claim 16, wherein said thickness is includedbetween {fraction (1/12)}th and ¼ of the length of the largest side ofsaid base.
 18. The method of claim 16, wherein said base has atriangular or trapezoidal shape.
 19. The method of claim 16, whereinsaid base is slightly incurved so that, once the implant is positioned,it follows a radius of curvature of the eye.
 20. The method of claim 14,wherein said implant presents substantially the shape of a prism withtrapezoidal base.
 21. The method of claim 20, wherein said implantpresents substantially the shape of a straight prism with trapezoidalbase.
 22. The method of claim 14, wherein the apices of said implant areblunt.
 23. The method of claim 14, wherein said hyaluronic acid has beencrosslinked, via its hydroxyl functions, by means of a crosslinkingagent presenting reactive functions; said agent intervening inquantities such that the ratio: total number of reactive functions ofsaid crosslinking agent/total number of disaccharidic repeating units ofthe molecules of hyaluronic acid, is included between 0.2 and
 1. 24. Themethod of claim 23, wherein said reactive functions of said crosslinkingagent are epoxy functions.
 25. The method of claim 14, wherein saidcrosslinked hyaluronic acid has at least one active principleincorporated therein.
 26. A deep sclerectomy implant made of crosslinkedhyaluronic acid having substantially the pre-formed shape of apolyhedron with at least five faces and a thickness of about 2 mm,wherein at least one face is structured to direct flow of the aqueoushumor.
 27. A method for reducing the intra-ocular pressure in the eye ofa mammalian patient, comprising: incising the sclera of an eye untilplumb with Schlemm's canal to generate a cavity in the deep scleral bed,and inserting an implant in said cavity, wherein said implant is made ofcrosslinked hyaluronic acid having substantially the shape of apolyhedron with at least five faces, to allow increased aqueous humoroutflow from the anterior chamber of the eye, and reduce the intraocularpressure.